SYNTHESES OF ACYCLIC ANALOGS OF DIDEMNIN-B

The syntheses of three modified peptide fragments of the cyclodepsipep tide didemnin B are reported. The HIP and isostatine (1st) units of th e didemnin B macrocycle were simplified to a Z-alanine residue and the ester linkage (through threonine of the tetrapeptide) was replaced wi th amide linkages through the amines of glycine, D-alanine and an ethy lenediamine linker. The latter permitted the attachment of a N-Me-D-Le u-Pro-Lac moiety to afford analogs 2, 3 and 4 respectively.